Three-Four Photon Transition Mn(II) Complex Monitoring Lysosome-Related ATP in Real Time via Fluorescence Lifetime Imaging.

Currently, in situ monitoring of the adenosine triphosphate (ATP) level in lysosomes is critical to understand their involvement in various biological processes, but it remains difficult due to the interferences of limited targeting and low resolution of fluorescent probes. Herein, we report a classic Mn(II) probe (FX2-MnCl2) with near-infrared (NIR) nonlinear (NLO) properties, accompanied by three-four photon transition and fivefold fluorescence enhancement in the presence of ATP. FX2-MnCl2 combines with ATP through dual recognition sites of diethoxy and manganese ions to reflect slightly fluorescence lifetime change. Through the synergy of multiphoton fluorescence imaging (MP-FI) and multiphoton fluorescence lifetime imaging microscopy (MP-FLIM), it is further demonstrated that FX2-MnCl2 displays lysosome-specific targeting behavior, which can monitor lysosome-related ATP migration under NIR laser light. This work provides a novel multiphoton transformation fluorescence complex, which might be a potential candidate as a simple and straightforward biomarker of lysosome ATP in vitro for clinical diagnosis.

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Successful retrieval of tip-embedded inferior vena cava filter using a modified forceps technique: case report.

BACKGROUND: The retrieval of inferior vena cava (IVC) filter is essential for preventing complications associated with the device. Advanced techniques have been developed to improve the success rate of retrieving tip-embedded filters. The forceps technique is frequently used to address this issue. CASE PRESENTATION: We present a case study of two patients who underwent a successful tip-embedded IVC filter retrieval using a modified forceps technique, which has not been previously reported. This technique involves using a wire loop under the filter tip and a forceps to grasp the filter shoulder. By pulling the wire loop and pushing the forceps in counterforce, the filter tip is straightened and aligned with the vascular sheath. The vascular sheath can then dissect the filter tip out from the caval wall and get inside the sheath to complete the retrieval. CONCLUSIONS: The modified forceps technique we present here offers a new solution for the complex retrieval of IVC filters.

Current status and value of testing antiphospholipid antibody in patients with acute ischemic stroke: a retrospective single-center study in China.

BACKGROUND AND PURPOSE: Testing for antiphospholipid antibodies (aPL) is useful to determine the cause of ischemic stroke in young and female patients. However, the clinical relevance of aPL in older patients with ischemic stroke remains unclear. We aimed to explore the status and diagnostic value of initial aPL testing in all patients with acute ischemic stroke. METHODS: We retrospectively analyzed patients with acute ischemic stroke who were consecutively hospitalized in our hospital between June 2012 and January 2022 and investigated the factors associated with performing aPL screening in real-world clinical practice. Furthermore, factors associated with initial aPL positivity were evaluated by comparing the demographic, etiological, and therapeutic characteristics. RESULTS: Of 1209 patients, 287 (23.7%) were tested for aPL and 58 (20.2%) tested positive. Physicians tended to conduct aPL testing on female patients (P<0.001), younger patients (P<0.001), patients with fewer vascular risk factors (P<0.001), and multiple infarctions in the multivascular blood supply area (P<0.001). Multivariate logistic regression analysis showed that only stroke of other determined etiology type was a significant influencing factor for positive aPL results (OR 2.97, 95% CI 1.137, 7.774, P=0.026), adjusting for sex, age, and causes of stroke, etc. CONCLUSION: Approximately one-quarter of the patients with acute ischemic stroke were tested for aPL. Age, sex, number of vascular risk factors, and neuroimaging features affected the discretion in performing aPL testing. aPL testing may be appropriate in older patients with no identified cause of ischemic stroke and may provide additional diagnostic opportunities for acute ischemic stroke.

"Catheter Kissing" Technique to Recanalize Chronic Total Occlusions in Iliac Artery with Wire-Catheter Approach.

BACKGROUND: To describe a technique in which 2 5-F curved catheters were used to facilitate the wire-catheter approach for recanalizing chronic total occlusions (CTOs) in the iliac arteries concurrently affecting the common iliac artery and external iliac artery. METHODS: This was a single-center retrospective analysis involving endovascular recanalization of 17 iliac artery CTOs in 15 patients (mean age: 73.66 years; all men) between January 2019 and October 2022 using the subintimal arterial flossing with antegrade-retrograde intervention technique. With antegrade and retrograde guidewires in the subintimal spaces of CTOs, the location where the 2 guidewires seemed to overlap was identified as the rendezvous point. Although the 2 guidewires appeared to be in close proximity, there was no evidence that the bidirectional subintimal channels were connected. If several initial attempts failed, 2 5-F multipurpose catheters were introduced to the rendezvous point, followed by twisting, pulling, and pushing maneuvers until the tips of the catheters touched, indicating that the bidirectional subintimal channels were joined. A second wire rendezvous attempt was then employed to create a flossing-type guidewire. Outcome measurements included technical success, rendezvous points, complications, and procedure duration. RESULTS: Among this cohort, 80.0% smoked and 66.7% had hypertension. In 11 limbs (64.7%), when initial wire rendezvous attempts failed, the "catheter kissing" technique was employed to successfully recanalize iliac artery CTOs, taking an average of 3.80 ± 1.64 min to complete the secondary wire rendezvous. The average length of CTOs was 111.06 ± 9.99 mm, with 7 (41.2%) and 8 (47.1%) cases exhibiting severe calcification and flush occlusion, respectively. The wire rendezvous point for all cases was in external iliac artery and the average time for successful secondary wire rendezvous was 3.80 ± 1.64 min. All patients were treated with iliac artery stents. No statistically significant difference was observed between the puncture sites of the common femoral artery and superficial femoral artery in relation to failure of the primary wire rendezvous (P = 0.644). No in-hospital deaths or complications were associated with the procedure, including iliac artery rupture, distal embolization, or access site complications. CONCLUSIONS: In patients with extensive iliac artery CTOs, the "catheter kissing" technique may offer an effective and time-efficient recanalization approach, without requiring additional specialized devices. Importantly, the risk of complications remains unchanged even when employing a wire rendezvous in a challenging subintimal space.

Efficient Recovery of Phosphate from Water Media by Iron-Magnesium Functionalized Lignite: Adsorption Evaluation, Mechanism Revelation and Potential Application Exploration.

Selective phosphorus removal from aquatic media has become an ideal strategy to mitigate eutrophication and meet increasingly stringent discharge requirements. To achieve phosphorus control and resource utilization of low-calorific-value lignite, iron and magnesium salts were used to functionalize lignite, and iron-magnesium functionalized lignite (called IM@BC) was prepared for phosphate recovery from water media. The adsorption properties of IM@BC were systematically evaluated, especially the influence of ambient pH and co-existing ions. The kinetic, isothermal, and thermodynamic adsorption behaviors of IM@BC were analyzed. The adsorption mechanism was revealed by microscopic characterization. The potential application of phosphate-containing IM@BC (P-IM@BC) was explored. The results show that IM@BC has a strong phosphate adsorption capacity, and the maximum adsorption capacity is 226.22 mgP/g at pH = 3. Co-existing CO32- inhibits phosphate adsorption, while coexisting Ca2+ and Mg2+ enhance the effect. At the initial adsorption stage, the amount of phosphate adsorbed by IM@BC continues to increase, and the adsorption equilibrium state is gradually reached after 24 h. The adsorption process conforms to the pseudo-second-order kinetic model (PSO) and Langmuir isothermal adsorption model, and the adsorption process is mainly chemical adsorption. The phosphate absorption capacity is positively correlated with temperature (283.15 K~313.15 K), and the adsorption process is spontaneous, endothermic, and entropy-increasing. Its adsorption mechanism includes electrostatic attraction, ion exchange, surface precipitation, and coordination exchange. IM@BC can efficiently recover phosphate from actual phosphorus-containing wastewater with a recovery efficiency of up to 90%. P-IM@BC slowly releases phosphate from pH 3 to 11. Plant growth experiments showed that P-IM@BC could be used as a slow-release fertilizer to promote the root growth of cowpeas. The novelty of this work lies in the development of a highly efficient phosphate recovery adsorbent, which provides a feasible method of phosphorus control in water media and resource utilization of lignite.

An LTR retrotransposon insertion inside CsERECTA for an LRR receptor-like serine/threonine-protein kinase results in compact (cp) plant architecture in cucumber.

The compact (cp) phenotype in cucumber (Cucumis sativus L.) is an important plant architecture-related trait with a great potential for cucumber improvement. In this study, we conducted map-based cloning of the cp locus, identified and functionally characterized the candidate gene. Comparative microscopic analysis suggested that the short internode in the cp mutant is due to fewer cell numbers. Fine genetic mapping delimited cp into an 8.8-kb region on chromosome 4 harboring only one gene, CsERECTA (CsER) that encodes a leucine-rich repeat receptor-like kinase. A 5.5-kb insertion of a long terminal repeat retrotransposon in the 22nd exon resulted in loss-of-function of CsER in the cp plant. Spatiotemporal expression analysis in cucumber and CsER promoter-driven GUS assays in Arabidopsis indicated that CsER was highly expressed in the stem apical meristem and young organs, but the expression level was similar in the wild type and mutant cucumber plants. However, CsER protein accumulation was reduced in the mutant as revealed by western hybridization. The mutation in cp also did not seem to affect self-association of CsER for formation of dimers. Ectopic expression of CsER in Arabidopsis was able to rescue the plant height of the loss-of-function AtERECTA mutant, whereas the compact inflorescence and small rosette leaves of the mutant could be partially recovered. Transcriptome profiling in the mutant and wild type cucumber plants revealed hormone biosynthesis/signaling, and photosynthesis pathways associated with CsER-dependent regulatory network. Our work provides new insights for the use of cp in cucumber breeding.

Topology Effects of Poly(2-ethyl-2-oxazoline) Brushes with Various Architectures for Antifouling Behavior under Shear Flow.

Polymer brushes with different topological architectures exhibit unparalleled interfacial and physicochemical properties and are being widely utilized in antifouling applications. However, there is an absence of a thorough understanding of the antifouling process of dynamic flow mediated by the topological structure of polymer brushes. Here, it is highlighted how the interface parameters related to biofouling in flowing carrier fluid are tuned by topologically different architectures. The mechanism by which three brushes with various topological structures (cyclic, looped, and linear brushes) encounter biological media was revealed by relating protein adhesion with nanomechanics and protein conformational transitions on poly(2-ethyl-2-oxazoline) (PEtOx) brushes. In contrast to the classically linear analogue, the cyclic PEtOx brushes confered an enhanced steric barrier and excellent lubrication at the critical density region. The impenetrable and smoother layer prevented the approach and shortened the residence time for protein on the surface, providing optimal antifouling properties at low shear rates. The looped brushes also significantly inhibited protein adhesion under prolonged high shear rates due to their unshakable conformational characteristics. These findings detailed a new evaluation framework behind polymer brushes of topology-driven biofouling repulsion under flow conditions and pointed the way toward a promising approach for the effectiveness of biomaterial design.

Acidity Scale in a Choline Chloride- and Ethylene Glycol-Based Deep Eutectic Solvent and Its Implication on Carbon Dioxide Absorption.

An equilibrium acidity (pKa) scale that comprises 16 Brönsted organic acids, including phenols, carboxylic acids, azoles, and phenylmalononitriles, was established in a choline chloride/EG-based deep eutectic solvent (DES) ([Ch][Cl]:2EG) by ultraviolet-visible (UV-Vis) spectroscopic methods. The established acidity scale spans about 6 pK units in the DES, which is similar to that for these acids in water. The acidity comparisons and linear correlations between the DES and other solvents show that the solvent property of [Ch][Cl]:2EG is quite different from those of amphiphilic protic and dipolar aprotic molecular solvents. The carbon dioxide absorption capabilities as well as apparent absorption kinetics for a series of anion-functionalized DESs ([Ch][X]:2EG) were measured, and the results show that the basicity of comprising anion [X] of choline salt is essential for the maximum carbon dioxide absorption capacity, i.e., a stronger basicity leads to a greater absorption capacity. The possible absorption mechanisms for carbon dioxide absorption in these DESs were also discussed based on the spectroscopic evidence.

Cation Substitution and Size Effects in Ca2ZnSb2 and Yb2MnSb2: Crystal and Electronic Structures and Thermoelectric Properties.

Zintl compounds often feature complex structural fragments and small band gaps, favoring promising thermoelectric properties. In this work, a new phase Ca2ZnSb2 is synthesized and characterized to be a LiGaGe-type structure. It is isotypic to Yb2MnSb2 with half vacancies at transition metal sites and undergoes a phase transition to Ca9Zn4+xSb9 after annealing. Interestingly, Ca2ZnSb2 and Yb2MnSb2 are amenable to diverse doping mechanisms at different sites. Here, by substituting smaller Li on cation sites, two novel layered compounds Ca1.84(1)Li0.16(1)Zn0.84(1)Sb2 and Yb1.82(1)Li0.18(1)Mn0.96(1)Sb2 with the P63/mmc space group are discovered, which can be viewed as derivatives of LiGaGe type. Despite having lower occupancy, the structural stability is improved compared with the prototype compounds owing to the reduced interlayered distances. Besides, the band structure analyses demonstrate that the bands near the Fermi level are mainly governed by the interlayered interaction. Due to the highly disordered structure, Yb1.82Li0.18Mn0.96Sb2 features ultralow thermal conductivity from 0.79 to 0.47 W·m-1·K-1 among the testing range; in addition, a remarkable Seebeck coefficient of 270.77 µV·K-1 at 723 K is observed. The discovery of the Ca2ZnSb2 phase enriches the 2-1-2 map, and the size effect induced by cations provides new ideas for material designing.

Sacubitril/Valsartan Can Reduce Atrial Fibrillation Recurrence After Catheter Ablation in Patients with Persistent Atrial Fibrillation.

PURPOSE: This study compared the effectiveness of sacubitril/valsartan (SV) vs. valsartan (V) for treating persistent atrial fibrillation (AF) after radio-frequency catheter ablation (RFCA). METHODS: Patients with persistent AF who received RFCA were randomly assigned to the SV or V treatment group with the intervention lasting for 12 months. The primary outcome included any atrial arrhythmia episode lasting ≥ 30 s after a 3-month blanking period. The secondary outcome included any atrial arrhythmia episode lasting ≥ 24 h or requiring cardioversion after a 3-month blanking period. The H2FPEF score was used to assess the possibility of patients suffering from heart failure with preserved ejection fraction. RESULTS: A total of 143 patients with persistent AF who received RFCA were randomized for the study, with 5 patients failing to follow-up. Among them, 29 (42%) out of 69 patients receiving V and 15 (21.7%) out of 69 patients receiving SV reached the primary endpoint (P < 0.001). A total of 26 (37.7%) out of 69 patients receiving V and 7 (10.1%) out of 69 patients receiving SV reached the secondary endpoint (P < 0.001). A decrease in the H2FPEF score after a 1-year follow-up seemed to be related to the recurrence of AF (OR, 0.065; 95% CI: 0.018-0.238, P < 0.001). CONCLUSIONS: SV can decrease AF recurrence after catheter ablation in patients with persistent AF at the 1-year follow-up. The mechanism for this process may be related to the reduction in the H2FPEF score in patients with preserved ejection fraction heart failure.

Dipeptidyl-peptidase-4 inhibitors have anti-inflammatory effects in patients with type 2 diabetes.

AIMS: Systematic low-grade inflammation is considered to be an important factor leading to the development of T2DM and the progression of its complications. Dipeptidyl-peptidase-4 (DPP-4) inhibitors show potential anti-inflammatory effects in patients with T2DM. This meta-analysis aimed to evaluate the anti-inflammatory effects of DPP-4 inhibitors in patients with T2DM. METHODS: A comprehensive search was performed in PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials that assess the anti-inflammatory effects of DPP-4 inhibitors. Quantitative data analysis was conducted by a random-effects model. Sensitivity analyses were conducted to determine the robustness of the pooled results. RESULTS: Twenty-two studies with 1595 patients with T2DM were included. Pooled results showed that DPP-4 inhibitor therapy was significantly associated with the reduction of C-reactive protein (CRP) (SMD, - 0.56, p < 0.01), TNF-α (SMD, - 1.69, p < 0.01), IL-6 (SMD, - 0.67, p < 0.01), and IL-1ß (WMD, - 8.21 pg/ml, p < 0.01). Leave-one-out meta-analysis showed no significant change in the pooled results of CRP and TNF-α. CONCLUSION: This meta-analysis demonstrated that DPP-4 inhibitors can significantly attenuate low-grade inflammatory state in patients with T2DM. In addition to improving glycemic control, DDP-4 inhibitors might offer extra therapeutic value by controlling inflammation.

An efficient strategy for large-scale preparation of low polarity gingerols directly from ginger crude extract by high-speed countercurrent chromatography with different rotation mode.

This study presents an efficient strategy for large-scale preparation of low polarity gingerols directly from ginger crude extract by high-speed countercurrent chromatography with different rotation mode. The ultrasonic-assisted extraction conditions were optimized by response surface methodology and the results showed the major low polarity gingerols could be well enriched under the optimized extraction conditions. Then the crude extract without any pretreatment was directly separated by high-speed countercurrent chromatography with different rotation mode using n-hexane/ethyl acetate/methanol/water (6:4:6:4, v/v/v/v) as the solvent system. In about 400 min, five major gingerols including 150 mg of [6]-gingerol, 50 mg of [8]-gingerol, 20 mg of [6]-shogaol, 43 mg of [6]-dehydrogingerdione, and 40 mg of [10]-gingerol were obtained from 1.2 g of crude extract in a single run with repeated injection. Their structures were identified by 1 H-NMR spectroscopy.

Small-angle measurement system enhanced by an optical phased array.

Small-angle measurement can be realized by embedding the laser beam in a reflective sector, within which multiple reflections enlarge the angle between the input and the output beams. However, the maximum detectable angle is limited by the detector aperture at the receiver side. In this work, we propose, to the best of our knowledge, a novel small-angle measurement system enhanced by an optical phased array (OPA), which is loaded on a spatial light modulator (SLM) to increase the maximum measurement range. The experimental results verify the effectiveness of the proposed system, and a wider measurement range with an unaffected measurement accuracy can be obtained. In the proof-of-concept demonstration, the measurement range of the system is enlarged by at least five times compared to the system without OPA, while maintaining the same measurement accuracy.

Cloning and expression of recombinant human superoxide dismutase 1 (hSOD1) in Bacillus subtilis 1012.

OBJECTIVE: We aimed to clone and express the human Cu, Zn superoxide dismutase (hSOD1) in Bacillus subtilis 1012. Also, we investigated the expression level of hSOD1 under different induction conditions. RESULT: As an essential member of the antioxidant defense system in vivo, hSOD1 has become a therapeutic agent against host diseases, such as oxygen toxicity, acute inflammation, and radiation injury. The recombinant hSOD1 was successfully secreted extracellularly into B. subtilis 1012. The expression conditions were optimized, including inoculum size, different media, temperatures, and inducer concentrations. Finally, the highest level of hSOD1 was produced as a soluble form in Super rich medium by 2% inoculum with 0.2 mM of IPTG at 37 °C after the induction for 24 h. Besides, 20 g/L of lactose also displayed the same inductive effect on hSOD1 expression as that of IPTG (0.2 mM). Finally, the specific activity of purified hSOD1 was determined to be 1625 U/mg in the presence of 800 µM of Cu2+ and 20 µM of Zn2+. CONCLUSIONS: We propose that the B. subtilis 1012-hSOD1 strain system has great potential in future industrial applications.

Clonal Outbreak of Trichophyton tonsurans Causing Tinea Capitis Among a Wrestling Team in Beijing, China.

Trichophyton tonsurans mostly causes tinea capitis and tinea corporis and often associates with outbreaks among combat sports athletes. Here, we report an outbreak of tinea capitis caused by T. tonsurans among five juvenile athletes in a wrestling team in Beijing, China. Scrapings from the lesions of the five patients were performed by direct microscopic examination and fungal culture. The fungal pathogens were all identified as T. tonsurans by morphology and sequencing of the internal transcribed spacer (ITS) regions. Multilocus genotyping analysis was performed by sequencing of 13 gene loci. The sequences of these markers were identical among the five isolates, revealing a single genotype. Antifungal susceptibilities of terbinafine, itraconazole, fluconazole, ketoconazole, and amphotericin B against T. tonsurans was determined by broth microdilution method according to the Clinical and Laboratory Standards Institute M38-A3 document and these isolates were all susceptible to the common antifungal drugs treating tinea capitis.

Performance and mechanism of co-culture of Monascus purpureus, Lacticaseibacillus casei, and Saccharomyces cerevisiae to enhance lovastatin production and lipid-lowering effects.

To facilitate lipid-lowering effects, a lovastatin-producing microbial co-culture system (LPMCS) was constituted with a novel strain Monascus purpureus R5 in combination with Lacticaseibacillus casei S5 and Saccharomyces cerevisiae J7, which increased lovastatin production by 54.21% compared with the single strain R5. Response Surface Methodology (RSM) optimization indicated lovastatin yield peaked at 7.43 mg/g with a fermentation time of 13.88 d, water content of 50.5%, and inoculum ratio of 10.27%. Meanwhile, lovastatin in LPMCS co-fermentation extracts (LFE) was qualitatively and quantitatively analyzed by Thin-Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). Cellular experiments demonstrated that LFE exhibited no obvious cytotoxicity to L-02 cells and exhibited excellent biosafety. Most notably, high-dose LFE (100 mg/L) exhibited the highest reduction of lipid accumulation, total cholesterol, and triglycerides simultaneously in oleic acid-induced L-02 cells, which decreased by 71.59%, 38.64%, and 58.85% than untreated cells, respectively. Overall, LPMCS provides a potential approach to upgrade the lipid-lowering activity of Monascus-fermented products with higher health-beneficial effects.

Stanniocalcin 2 is induced by estrogen and promotes growth in endometrial cancer via AMPK pathway.

Stanniocalcin 2 (STC2) is identified as a glycosylated peptide hormone and estrogen-responsive gene in cancer cells. STC2 participates in angiogenesis, cell development, cytoprotection, and calcium and phosphate regulation during the development of cancer. The role of STC2 in endometrial cancer (EC) remains unclear. The data from the bioinformatic and immunohistochemical analysis showed that STC2 was upregulated in the EC tissues. The EC cells were treated with 17ß-estradiol (E2), and 0.1 µmol/L E2 increased the expression of STC2 in the EC cells. E2 also increased cell viability, promoted proliferation, and inhibited apoptosis of EC. However, the knockdown of STC2 decreased cell viability, reduced proliferation, and promoted apoptosis of E2-stimulated EC. Moreover, silencing of STC2 attenuated E2-induced downregulation of phosphorylated-AMP-activated protein kinase (AMPK) in the EC cells. The loss of STC2 reduced E2-stimulated tumor growth EC in vivo. In conclusion, STC2 deficiency suppressed E2-stimulated proliferation and tumor growth of EC through the activation of AMPK signaling.

DOIDS: An Intrusion Detection Scheme Based on DBSCAN for Opportunistic Routing in Underwater Wireless Sensor Networks.

In Underwater Wireless Sensor Networks (UWSNs), data should be transmitted to data centers reliably and efficiently. However, due to the harsh channel conditions, reliable data transmission is a challenge for large-scale UWSNs. Thus, opportunistic routing (OR) protocols with high reliability, strong robustness, low end-to-end delay, and high energy efficiency are widely applied. However, OR in UWSNs is vulnerable to routing attacks. For example, sinkhole attack nodes can attract traffic from surrounding nodes by forging information such as the distance to the sink node. In order to reduce the negative impact of malicious nodes on data transmission, we propose an intrusion detection scheme (IDS) based on the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) clustering algorithm for OR (DOIDS) in this paper. DOIDS is based on small-sample IDS and is suitable for UWSNs with sparse node deployment. In DOIDS, the local monitoring mechanism is adopted. Every node in the network running DOIDS can select the trusted next hop. Firstly, according to the behavior characteristics of common routing attack nodes and unreliable underwater acoustic channel characteristics, DOIDS selected the energy consumption, forwarding, and link quality information of candidate nodes as the detection feature values. Then, the collected feature information is used to detect potential abnormal nodes through the DBSCAN clustering algorithm. Finally, a decision function is defined according to the time decay function to reduce the false detection rate of DOIDS. It makes a final judgment on whether the potential abnormal node is malicious. The simulation results show that the algorithm can effectively improve the detection accuracy rate (3% to 15% for different scenarios) and reduce the false positive rate, respectively.

Sp1 Upregulation Bolsters the Radioresistance of Glioblastoma Cells by Promoting Double Strand Breaks Repair.

Radioresistance remains a critical obstacle in the clinical management of glioblastoma (GBM) by radiotherapy. Therefore, it is necessary to explore the molecular mechanisms underlying radioresistance to improve patient response to radiotherapy and increase the treatment efficacy. The present study aimed to elucidate the role of specificity protein 1 (Sp1) in the radioresistance of GBM cells. Different human GBM cell lines and tumor-bearing mice were exposed to ionizing radiation (IR). Cell survival was determined by the colony formation assay. The expression of genes and proteins in the cells and tissues was analyzed by RT-PCR and western blotting, respectively. The γ-H2AX, p-Sp1 and dependent protein kinase catalytic subunit (DNA-PKcs phospho S2056) foci were analyzed by immunofluorescence. Apoptotic rates were measured by flow cytometry. Sp1 was upregulated after IR in vitro and in vivo and knocking down Sp1-sensitized GBM cells to IR. Sp1 activated the DNA-PKcs promoter and increased its expression and activity. Furthermore, the loss of Sp1 delayed double-strand breaks (DSB) repair and increased IR-induced apoptosis of GBM cells. Taken together, IR upregulates Sp1 expression in GBM cells, enhancing the activity of DNA-PKcs and promoting IR-induced DSB repair, thereby leading to increased radioresistance.